Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0835 or +27 21 938 0967
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202609673560343 Date of Registration: 11/09/2026
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Evaluation of host and mycobacterial biomarkers that can serve as systemic measures of pathogen load in a BCG-orientated human lung challenge model (TB-LOAD)
Official scientific title Evaluation of host and mycobacterial biomarkers that can serve as systemic measures of pathogen load in a BCG-orientated human lung challenge model (TB-LOAD)
Brief summary describing the background and objectives of the trial Development and evaluation of a new TB vaccine or drug including licensing the product costs almost a billion pounds per vaccine or drug developed. However, with new TB vaccines, evaluation is particularly difficult as there is no established correlate of protection. This is likely critical, as prioritising one vaccine or drug over another (rapidity of pathogen clearance) will depend on developing a systemic measure of pathogen load as TB causes disease in several compartments in tandem (e.g. lung interstitium, alveolar space, lymph nodes, pleura, liver, spleen etc). We hypothesize that longitudinal compartment-specific mycobacterial load can be measured in healthy volunteers using a combination of mycobacterial and host biomarkers after dose-specific lung challenge with nebulised or bronchoscopically instilled BCG. Aim 1. To generate a sample biobank, for evaluation of current and future assays, by recruiting a cohort of healthy volunteers challenged with BCG (both nebulized and bronchoscopic; N=72) Aim 2. To measure host biomarkers (blood transcriptomics) and pathogen biomarkers (serum LAM, cell free DNA and extracellular vesicles) in the blood compartment over an 8-week period. Aim 3. To measure pathogen (lipid biomarkers, urine LAM and extracellular vesicle) and host biomarkers (protein/peptide biomarkers) in the urine compartment at serial timepoints over an 8-week period. Aim 4. To evaluate pathogen (16s rRNA, Path Fast BAL/sputum LAM, Xpert Ultra, MGIT culture) and host (BAL/sputum transcriptomic and soluble proteins) biomarkers in the respiratory tract compartment (induced sputum, BAL, nasal wash, exhaled breath). Aim 5. To use data from aims 2 to 4 to construct a biomarker and compartment-specific longitudinal reference standard using the BCG lung challenge model.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) TB LOAD
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Tuberculosis
Purpose of the trial Treatment: Drugs
Anticipated trial start date 01/07/2026
Actual trial start date
Anticipated date of last follow up 30/06/2029
Actual Last follow-up date
Anticipated target sample size (number of participants) 122
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
DOH-27-092026-7091 SANCTR
TB-LOAD UCT HREC
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Simple randomization using a randomization table created by a computer software program Allocation Sequence/Code was not concealed Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Bronchoscopic instillation of BCG 3 doses: n=12 in each group: 1x10^3 CFU 1x10^4 CFU 1x10^5 CFU Single Bronchoscopic instillation of BCG 36
Experimental Group Nebulized instillation of BCG 3 doses, n=12 in each group: 1x10^6 CFU 1x10^7 CFU 1x10^8 CFU Single administration Nebulized instillation of BCG 36
Control Group Observation and sample collection from pulmonary tuberculosis patients - - Observation and non-invasive sample collection from pulmonary tuberculosis patients 50 Uncontrolled
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Is male or female aged 18 through 50 years on Study Day 1. 2. Has completed the written (or thumb printed and witnessed) informed consent process before any study-related procedures were performed. 3. Participants who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., to stay in contact with the CLII (CRC), return for follow-up visits) 4. Has general good health as confirmed by medical history and physical examination. 5. All participants born female who are engaging in sexual activity that could lead to pregnancy must commit to use an acceptable method of contraception from 21 days prior to Study Day 1 and for the 2 months after BCG administration. 6. All male participants should agree to use barrier contraception with their female partners for at least 2 weeks after BCG administration. 7. No TB contact* or receipt of tuberculin skin test in the 6 months prior to Study Day 1. 8. Has a positive IGRA test result at screening. 9. HIV negative at screening. 10. Negative clinical screening questionnaire, Xpert MTB/RIF negative sputum sample, and normal chest x-ray for pulmonary TB disease at screening. 1. Age <18 years. 2. HIV co-infection. 3. Smoker (or ex-smoker less than 2 years since quitting) 4. Acute illness and/or axillary temperature ≥37.5°C on Study Day 1. 5. Current suspicion or evidence (including but not limited to sputum Xpert MTB/RIF positive) of active TB disease at any CRC. An attempt must be made to obtain sputum from each participant; persons who are sputum unproductive will be assumed to be TB disease negative. 6. Abnormal CXR. 7. History of previous TB disease and/or treatment for TB disease. 8. Receipt of TB preventative therapy within 28 days prior to Study Day 1. 9. Received any investigational drug or investigational vaccine within 42 days before Study Day 1, or planned use during the study period. 10. Planned administration/administration of a licensed vaccine not foreseen by the study protocol in the period starting 28 days before Study Day 1 and ending 28 days after BCG administration. 11. Prior receipt of any investigational TB vaccine candidate before Study Day 1**. 12. Chronic administration of immunosuppressive medication within 42 days before Study Day 1 (inhaled and topical corticosteroids are permitted). 13. Any confirmed or suspected immunosuppressive, immunodeficient, or autoimmune condition based on medical history and physical examination (no laboratory testing required). 14. Concurrent, or planned participation in any other investigational study during the study period. (Concurrent participation in an observational trial not requiring blood or tissue sample collection is not an exclusion.) 15. Received immunoglobulin or blood products within 42 days before Study Day 1, or planned administration during the study period. 16. History of any reaction or hypersensitivity likely to be exacerbated by any component of the BCG vaccine. 17. Pregnant or lactating/nursing female, or positive urine pregnancy test during screening or pre-vaccination on Study Day 1. 18. Any current, or history of, medication use or medical, psychiatric, oc Adult: 18 Year(s)-44 Year(s) 18 Year(s) 50 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 30/07/2026 University of Cape Town Lung Institute
Ethics Committee Address
Street address City Postal code Country
Anzio Road Cape Town 7000 South Africa
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 23/06/2026 SAHPRA
Ethics Committee Address
Street address City Postal code Country
CSIR Reception Building 38a Meiring Naudé Road Brummeria Pretoria Pretoria 0083 South Africa
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Pathogen- and host-specific biomarkers in the blood compartment (i) cfDNA (ii) serum LAM (iii) Host transcriptomic profile (iv) Extracellular vesicle readouts Day 0, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 57
Primary Outcome Pathogen- and host-specific biomarkers in the respiratory compartment: (i) 16S rRNA (ii) PATHFAST LAM (iii) Xpert/ddPRC read-out (iv) MGIT culture (v) Soluble proteins (e.g. cytokines) Day 0, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 57
Primary Outcome Pathogen- and host-specific biomarkers in the urine compartment: (i) LAM (ii) Pathogen- and host-proteomic profile (iii) Pathogen-associated lipidomic profile (iv) Extracellular vesicle readouts Day 0, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 57
Secondary Outcome Safety - Adverse events Throughout the trail
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Klipfontein subdistrict Klipfontein road Cape Town 7750 South Africa
FUNDING SOURCES
Name of source Street address City Postal code Country
The Wellcome Trust 215 Euston Road, Gibbs Building, London NW1 2BE United Kingdom
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor University of Cape Town Lung Institute George Street Mowbray 7700 South Africa University
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Aliasgar Esmail ali.esmail@uct.ac.za 0789044492 H47 Old Main Building, Groote Schuur Hospital, Groote Schuur road
City Postal code Country Position/Affiliation
Observatory 7925 South Africa Deputy head of the Centre for Lung Infection and Immunity
Role Name Email Phone Street address
Public Enquiries Suzette Oelofse suzette.oelofse@uct.ac.za +27832488557 H36 old main Building, Groote Schuur Hospital, Observatory
City Postal code Country Position/Affiliation
Cape Town 7925 South Africa Deputy head of the Clinical Trials Unit
Role Name Email Phone Street address
Scientific Enquiries Shameem Jaumdally shameem.jaumdally@uct.ac.za +27825086252 H26 old main Building, Groote Schuur hospital, Observatory
City Postal code Country Position/Affiliation
Cape Town 7925 South Africa Senior scientist
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Individual Participant Data will be made available to researchers who provide a protocol that is approved by their respective human research ethics committee. Study Protocol Up to five years following publication. All protocols/proposals will be reviewed and approved by the trial steering committee up to five years following publication. A data sharing agreement (DTA) will need to be concluded between the representatives of the requesting institution and the University of Cape Town. Data sharing requests should be directed to the PI: ali.esmail@uct.ac.za
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information